Copy number variations in urine cell free DNA as biomarkers in advanced prostate cancer. Oncotarget 2016 Jun 14;7(24):35818-35831
Date
04/30/2016Pubmed ID
27127882Pubmed Central ID
PMC5094965DOI
10.18632/oncotarget.9027Scopus ID
2-s2.0-84978062670 (requires institutional sign-in at Scopus site) 56 CitationsAbstract
Genetic profiling of urine cell free DNA (cfDNA) has not been evaluated in advanced prostate cancer. We performed whole genome sequencing of urine cfDNAs to identify tumor-associated copy number variations in urine before and after initiating androgen deprivation therapy in HSPC stage and docetaxel chemotherapy in CRPC stage. A log2 ratio-based copy number analysis detected common genomic abnormalities in prostate cancer including AR amplification in 5/10 CRPC patients. Other abnormalities identified included TMPRSS2-ERG fusion, PTEN gene deletion, NOTCH1 locus amplification along with genomic amplifications at 8q24.3, 9q34.3, 11p15.5 and 14q11.2, and deletions at 4q35.2, 5q31.3, 7q36.3, 12q24.33, and 16p11.2. By comparing copy number between pre- and post-treatment, we found significant copy number changes in 34 genomic loci. To estimate the somatic tumor DNA fraction in urine cfDNAs, we developed a Urine Genomic Abnormality (UGA) score algorithm that summed the top ten most significant segments with copy number changes. The UGA scores correlated with tumor burden and the change in UGA score after stage-specific therapies reflected disease progression status and overall survival. The study demonstrates the potential clinical utility of urine cfDNAs in predicting treatment response and monitoring disease progression.
Author List
Xia Y, Huang CC, Dittmar R, Du M, Wang Y, Liu H, Shenoy N, Wang L, Kohli MMESH terms used to index this publication - Major topics in bold
AgedAndrogen Antagonists
Antineoplastic Agents
Biomarkers, Tumor
Cell-Free Nucleic Acids
Chromosome Aberrations
DNA Copy Number Variations
DNA, Neoplasm
Humans
Kaplan-Meier Estimate
Male
Middle Aged
PTEN Phosphohydrolase
Prostatic Neoplasms
Receptor, Notch1
Receptors, Androgen
Taxoids
